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Journal of Virology, May 2003, p. 5266-5274, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5266-5274.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Genome Delivery and Ion Channel Properties Are Altered in VP4 Mutants of Poliovirus

Pranav Danthi,1 Magdalena Tosteson,2 Qi-han Li,1,{dagger} and Marie Chow1*

Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205,1 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 021152

Received 21 November 2002/ Accepted 30 January 2003

During entry into host cells, poliovirus undergoes a receptor-mediated conformational transition to form 135S particles with irreversible exposure of VP4 capsid sequences and VP1 N termini. To understand the role of VP4 during virus entry, the fate of VP4 during infection by site-specific mutants at threonine-28 of VP4 (4028T) was compared with that of the parental Mahoney type 1 virus. Three virus mutants were studied: the entry-defective, nonviable mutant 4028T.G and the viable mutants 4028T.S and 4028T.V, in which residue threonine-28 was changed to glycine, serine, and valine, respectively. We show that mutant and wild-type (WT) VP4 proteins are localized to cellular membranes after the 135S conformational transition. Both WT and viable 4028T mutant particles interact with lipid bilayers to form ion channels, whereas the entry-defective 4028T.G particles do not. In addition, the electrical properties of the channels induced by the mutant viruses are different from each other and from those of WT Mahoney and Sabin type 3 viruses. Finally, uncoating and/or cytoplasmic delivery of the viral genome is altered in the 4028T mutants: the 4028T.G lethal mutant does not release its genome into the cytoplasm, and genome delivery is slower during infection by mutant 4028T.V 135S particles than by mutant 4028T.S or WT 135S particles. The distinctive electrical characteristics of the different 4028T mutant channels indicate that VP4 sequences might form part of the channel structure. The different entry phenotypes of these VP4 mutants suggest that the ion channels may be related to VP4's role during genome uncoating and/or delivery.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 W. Markham, Slot 511, Little Rock, AR 72205. Phone: (501) 686-5155. Fax: (501) 686-5362. E-mail: chowmarie{at}uams.edu.

{dagger} Present address: Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, People's Republic of China.

Journal of Virology, May 2003, p. 5266-5274, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5266-5274.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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